These studies are designed to extend our information about the circadian control of normal hard tissue metabolism in growing animals, and to gain insight about the long term consequences of pharmacologic intervention at different clockhours. Preliminary data in rats that the osteoinductive response to decalcified bone allografts might be due to differential immunologic responses were seen in corticosteroid animals, but it was contraindicated by a similar chronobiologic response to grafts which had been exhaustively extracted to deplete their immunogenic glycoprotein components. Of the studies involved, the rhythm of hemostasis, PTH activity and a chronotherapeutic response in joint tissues of rats injected with streroids. Our major objectives are now to explore further the variations in (1) parathyroid cell activity, (2) the chronoresponsitivity of bone cells and chondrocytes in laboratory animals to metabolic stressors such as premarin and steroids and antigenic stimuli, (3) to learn how immobilization can dissociate metabolic rhythms in various tissues of long bones, and (4) homostatic mechanisms. In each of these categories, rats, mice or rabbits will be entrained to a 12/12 hr. light-dark cycle three weeks prior to study, and different groups will be treated at intervals of 4 hours in a total 24 hr. period. Cartilage and bone matrix formation (collagen, hexosamine) will be studied radioisotopically and by non-radiotracers such as tetracycline. Biochemistry will be accomplished by routine microchemical methods. Chronotherapeutic regimens will be tested in rats exposed to hormones on a daily or alternate day regimen to augment the clinical relevance of these studies. BIBLIOGRAPHIC REFERENCES: Holtzman, R.B. and Simmons, D.J.: The macrodistribution of 226Ra in the skeleton of a radium dial painter. In: The Health Effects of Plutonium and Radium. (ed. W.S.S. Jee). J.W. Press, Salt Lake City, Utah, 1976, pp. 421-436. Simmons, D.J., Bratberg, J.J., Lesker, P.A., and Aab, L.: What is the best time of day to schedule a bone graft operation? Clin. Orth. 116:227-239, 1976.